TV Program DescriptionOriginal PBS Broadcast Date: October 16, 2007

Scientists have long puzzled over the different
fates of identical twins: both have the same genes, yet only one may develop a
serious disease like cancer or autism. What's going on? Does something
else besides genes determine who we are? NOVA explores this startling
possibility in this program.

The "something else" turns out to be a
network of chemical switches that sit on our DNA, turning genes off and on.
Called collectively the epigenome, the switches appear to play a major role in
everything from how our cells keep their identity to whether we contract dread
diseases. Epigenetic switches may even help mold our personalities—or so
it appears to Canadian researchers studying a group of epigenetically modified
rats.

"We're in the midst of probably the
biggest revolution in biology, which is going to forever transform the way we
understand genetics, environment, the way the two interact, and what causes
disease," says Mark Mehler, Professor of Neurology at Albert Einstein
College of Medicine. "It's another level of biology, which for the
first time really is up to the task of explaining the biological complexity of
life."

In this program, NOVA reveals the
clues that have led scientists to this new picture of genetic control and
expression. One such clue is the surprisingly modest number of genes that turned
up when technology made it possible to map the human genome. The Human Genome
Project was originally expected to find at least 100,000 genes defining the
human species. Instead the effort yielded only about 20,000—about the
same number as in fish or mice—too few, some believe, to account for
human complexity.

Researchers now suspect that it's how genes are
regulated that distinguishes species. What turns them on and off? Among other
things, epigenetic switches (though not all switches are epigenetic—see Gene Switches).

Another clue is that a single abnormality in a
chromosome may result in two completely different diseases, depending on
whether the defect is inherited from the mother or the father. The different
fates may be due to different settings of epigenetic switches.

And still another clue comes from a strain of mice
that eats without limit if given the chance, which leads to obesity,
diabetes, and cancer. Amazingly, their young can be rendered slim, healthy, and
longer-lived through a change in diet that leaves their genes intact but alters
their epigenetic switches (see A Tale of Two Mice).

The program closes at the controversial cutting
edge of this burgeoning new field. At the M. D. Anderson Cancer Center in Houston,
Texas, researchers are investigating epigenetic means to treat a deadly form of
leukemia (see Epigenetic Therapy).
In Washington State, a researcher finds that
a toxin given to rats still affects their offspring four generations later,
without producing any changes in their genes. And in Sweden, a study of
historical records seems to show that the lifespan of grandchildren is affected
by their grandparents' access to food.

Might these effects be epigenetic? Might our
experiences, by changing our epigenomes, literally change the fate of our
offspring ... and their
offspring ... and theirs in turn? And might our own states of health owe
something to the diets and exposures of our forebears?

Some researchers are already convinced. "You
live your life as a sort of ... guardian of your genome," says Marcus
Pembrey of the Institute of Child Health at University College London, a
co-investigator in the Swedish study. "It seems to me you've got to
be careful of it because it's not just you. You can't be selfish
... you can't say, 'Well, I'll smoke' or
'I'll do whatever it is because I'm prepared to die
early.' You're also looking after it for your children and
grandchildren...." Epigenetics, Pembrey says, "is changing the
way we think about inheritance forever."

The epigenome is a kind of "second genome" that, among much else, may account for the surprising differences that can accumulate over time in identical twins even though they share exactly the same DNA.